beta-CIT SPECT demonstrates blockade of 5HT-uptake sites by citalopram in the human brain in vivo.
ABSTRACT The cocaine analogue 2-beta-carbomethoxy-3-beta-(4-iodophenyl)-tropane (beta-CIT) is a potent ligand for both dopamine- and serotonin uptake sites which in its 123I labeled form can be used for single photon emission computerized tomography (SPECT). It was demonstrated previously by SPECT-studies in non-human primates that 123I-beta-CIT binds to dopamine transporters in the striatum and to serotonin transporters in hypothalamus and midbrain. The aim of the present study was to compare 123I-beta-CIT binding in the brain stem of normal controls and a group of subjects under treatment with the selective serotonin reuptake inhibitor (SSRI) citalopram. 123I-beta-CIT-SPECT was performed in 12 depressed patients under 20 mg (n = 5), 40 mg (n = 6) and 60 mg (n = 1) citalopram daily, in one untreated depressed patient and in 11 controls at regular time intervals up till 24 hours p.inj. A highly significant reduction of beta-CIT binding was found in an area including mesial thalamus, hypothalamus, midbrain and pons in patients under citalopram compared to controls (44.1 +/- 14.4 vs. 82.3 +/- 18.6cpm's/mCi x kg body weight; specific binding 4 hrs p.inj.; p = 0.0001). No differences were seen between the high and low dose group and no changes were found in the striatum. 123I-beta-CIT binding in the brain stem and striatum in one untreated depressed patient fell within the range of control values. To our knowledge this is the first report directly demonstrating the effect of a selective serotonin uptake inhibitor in the brain in humans in vivo. SPECT measurements of serotonin uptake sites in patients with depression and other psychiatric disorders might provide better insights into the pathophysiology of these disorders and into mechanisms of drug action.
SourceAvailable from: Charles B Nemeroff[Show abstract] [Hide abstract]
ABSTRACT: Background: Prior research has suggested reductions in the density of serotonin transporter (SERT) binding sites in blood platelets and post-mortem brain tissue of depressed patients. We sought to determine whether patients with unipolar major depression have diminished SERT availability as assessed by both brainstem [123I]β-CIT SPECT and platelet [3H]paroxetine binding.Methods: Drug-free depressed and healthy subjects were injected with 211 ± 22 MBq [123I]β-CIT and imaged 24 ± 2 h later under equilibrium conditions. A ratio of specific to nonspecific brain uptake (V3″ = (brainstem-occipital)/occipital), a measure proportional to the binding potential (Bmax/Kd), was used for all comparisons.Results: Results showed a statistically significant reduction in brainstem V3″ values in depressed as compared to healthy subjects (3.1 ± .9 vs. 3.8 ± .8, p = .02). Platelet [3H]paroxetine binding was not altered (Bmax = 2389 ± 484 vs. 2415 ± 538 fmol/mg protein, p = .91) and was not significantly correlated with brainstem [123I]β-CIT binding (r = −0.14, p = .48).Conclusions: These data are the first to suggest reductions in the density of brain SERT binding sites in living depressed patients. These findings provide further support for a preeminent role for alterations in serotonergic neurons in the pathophysiology of depression.Biological Psychiatry 12/1998; 44(11):1090-1098. DOI:10.1016/S0006-3223(98)00272-8 · 9.47 Impact Factor
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ABSTRACT: We review the conflicting results from imaging studies of dopamine transporter availability in depressed patients and also discuss the heterogeneity of the variables involved. Major depression includes diverse clinical manifestations and in recent years there has been an increasing interest in the identification of homogeneous phenotypes and different clinical subtypes of depression, e.g anhedonic depression, retarded depression, etc. In addition, the use of different radioligands and imaging techniques, diverse rating scales, together with the lack of control of clinical variables (clinical course, recent or past use of substances of abuse, etc.) make it difficult to clearly identify neuronal regions or networks with consistently abnormal structures or functions in major depressive disorder. It is probably necessary to build a shared approach between clinicians and researchers in order to identify standardized procedures to better understand the role of the dopamine transporter in depression. We outline a list of major issues and also suggest some standardised procedures in collecting clinical and imaging data on major depressed patients. Our aim is to delineate a possible "modus operandi" that would be a proposal for neuroreceptor studies on major depression.Journal of Psychiatric Research 12/2013; DOI:10.1016/j.jpsychires.2013.12.006 · 4.09 Impact Factor
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ABSTRACT: Genetic, epigenetic and environmental factors have been shown to influence serotonergic neurotransmission implicated in psychiatric and neurologic disorders. Due to the prominent effects of serotonin reuptake inhibition on negative mood states, a series of studies examined central serotonin transporter (5-HTT) availability and turnover in patients suffering from major depression, anxiety, obsessive-compulsive disorder and alcohol dependence. Human studies and animal experiments in rodents and non-human primates identified effects of genetic, epigenetic and environmental factors that modulate 5-HTT mRNA transcription and in vivo availability. In this chapter we review the literature and discuss studies in non-human primates that underwent social stress and displayed a reduction of the serotonin turnover rate among carriers of one or two short alleles of a functional polymorphism of the 5-HTT regulatory region. Further studies in these primates suggested specific effects of stress hormone responses on serotonin transporter availability depending on 5-HTT genotype and gender. In humans suffering from negative mood states such as depression or alcoholism, reduced availability of brainstem and thalamic serotonin transporters was associated with anxiety and may reflect stress exposure mediated by epigenetic interactions between stress hormone levels, gender and 5-HTT genotype that bias central processing of emotionally salient information.Handbook of Behavioral Neuroscience 01/2010; 21:731-748. DOI:10.1016/S1569-7339(10)70108-9